Amino-alcohol esters of aralkyloxy-benzoic acids



Patented Feb. 4, 1947 UNITED STATES PATENT OFFICE AMiNo-ALcoHoL ESTERS F ARALKYL- OXY-BENZOIC ACIDS Walter G. Christiansen, Glen Ridge, and Sidney E. Harris, Nutley, N. J., assignors to -E. R. Squibb & Sons, New York, N. Y., a corporation of New York No Drawing. Original application September 9,

1937, Serial No. 163,034. Divided and this application June 28, 1944, Serial No. 542,621

" 3 Claims.

:This application is a division of our application Serial No. 163,034, filed September 9, 1937. i This invention relates to, and has for its obj'ect-the provision of, certain amino-alcohol esters of oxy-benzoic acids, and acid-addition salts thereof. These esters have the general formula 0 ll RCHr-O G(l1alogen) wherein R and R have the above-noted signification, is reacted with an alcohol of the formula HOR"N y l wherein R" has the above-designated meaning, to produce the desired ester. However,. other methods hereinafter described may be employed to produce the compounds of the present invention.

The amino-esters of this invention are generally recovered in the form of their additionsalts with hydrochloric acid. However, other acids forming addition-salts with amines may be used in place of hydrochloric; such acids are boric, nitric, lactic, tartaric, citric, phosphoric, sulfuric, picric, and picrolonic. The addition salts may be converted into the free bases in the usual manner.

The following examples are illustrative of the invention:

EXAMPLE 1 Gamma-dimethylamino-n-propyl ester of p-(pphenyl-ethoxwbenzoic acid (hydrochloride) To 15.2 g. of methyl p-hydroxy-benzoate dissolved in a solution of 2.5 g. of metallic sodium 2 in 90 cc. of absolute alcohol, is added 20.5 g. of

p-phenyl-ethyl bromide, and the mixture is re-.

fluxed 7 hours. Filtering ofi the inorganic salts, distilling off the alcohol from the filtrate, hy-

drolyzing the residue by boiling it with aqueous.

alkali, precipitating the free acid with hydrogen chloride, filtering, washing and drying, yields the intermediate, p-(fl-phenyl-ethoxy) -benzoic acid, in the form of a white powder, melting at 163-164 C. Dissolving 10 g. of this intermediate compound in 40 cc. of phosphorus oxychloride, adding 8.6 g. of phosphorus pentachloride, warming the mixture on a steam bath, evaporating off th excess phosphorus oxychloride, and vacuumsdistilling the residue, yields the: acid chloride of the intermediate, having a boiling point (with slight decomposition) of 215-230 C./5 mm.

1.55 g. gamma-dimethylamino-propanol and 4.0g. p-(p-phenyl-ethoxy)-benzoyl chloride are dissolved'in chloroform and the solution is refluxed for a few minutes. Dry ether is added until a faint precipitate appears, and the whole is allowed to stand for some time. The crystalline precipitate formed is filtered off and washed with dry ether; it melts at 156.5-157.5 C. (corrected).

EXAMPLE 2 0 ,B-diethyZamino-ethyl ester of p-(p'-nitro-benzyloxy) benzoic acid (hydrochloride) EXAMPLE 3 p-diethyZamino-ethyl ester of p-(p-amino-benzyloxy) -benzoic acid (mono-hydrochloride) 5 g. ,c-diethylamino-ethyl ester of p-(p'-nitrobenzyloxy)-benzoic acid hydrochloride is dissolved in absolute alcohol and shaken with hydrogen gas in the presence of Adams platinum oxide catalyst (Org. Syn, Col. vol. page 452); until no more hydrogen is absorbed. The catalyst is then removed by filtration and dry ether added to precipitate the hydrochloride; on reabove:

4. p-Diethylamino-ethyl ester of p-(fi-phenylethoxy) b enaoic acid. I

5. c m-Di(dimethylaminomethyl) -amyl ester or p-(p-phenyl-ethoxy) -benzoic acid.

6. a-Methyl-a-dimethylaminomethyl gamma;- phenyl-n-propyl ester of p-(B-phenyl-ethoxwbenzoic acid.

7. Gamma-dimethylamino-n-propyl ester of 3- methyl-l-(B-phenyl-ethoxy) -bnzoic acid. 7

8. u-Methyl-a-dimethylaminomethyl n amyl ester of 3-methyl-4- (B-phenyl-ethoxy) -benzoic acid. a

9. u-Methyl-a-dimethylaminomethyl gammaphenyl-n-propyl ester of '3-methyl-4- .}3-phenylethox-yfibenzoic acid.

10. Methyl a dimethylaminomethyl-n amyl ester of p-(fi-phenyl-ethoxy) -benzoic acid.

11. 00,0; -di(dimethylaminomethyl) gammaphenyl-n-propyl ester of 3-methyl-4-(p-phenyl ethoXw-b'enzoic acid.

12. t u-Di(dimethylaminomethyl) n e amyl ester of 3-inethy1-4- (ii-phenyl-ethoxy) -benz6ic acid. r 7

EXAMPLE 13 Theintermediate 3 methyl-44,8 phenylethoxy) -benzoy-l chloride used in the preparation ofgthe. compoundsv of Examples 7, 8, 9,11 and 12 may be prepared as follows:

23 g. 'of the ethyl ester of 3-methyl-4-hydroxybenzoic acid, 3.2 g. sodium and 23 g. of p-phenylethyl bromide are reacted together in 200 cc. absolute alcohol in the manner described in Example 1. .The product 3-methyl-4- (p-phenyb- 4 ethoxy)-benzoic acid melts at 150-152 C. (corrected).

. 13 g. of this acid reacted with 10.5 g. phosphorus pentachloride in the manner described in Example 1 gives the corresponding-acid chloride boiling at 210215 C. at 1.0 mm.

The invention may be variously otherwise embodied, within the scope of the appended claims.

We claim:

1. The hydrochloride of gamma dimethylaminon propyl p (fi phenyl-ethoxy) -benzoate.

2. fl- Diethylax-nir'io-ethyl ester of p-(p-phenyl- 'ethoXy) be'nz'oid acid.

3. A compound of the group consisting of: amino-esters of the. general formula wherein R represents a member of, the group consisting of hydrogen and methyl, R repree sents a divalent alkyl residue with 2 to '3. carbon atoms, and RJ'" represents an alkyl residue with 1 to 2 carbon atoms; and acid-addition salts thereof. V

WALTER. G. CHRISTIANSEN. SIDNEY E. HARRIS.

REFERENCES crrED The following references are of record in the file of this patent:

UNITED STATES PATENT "S Number Na-me pate vi 2,103,266 Lott Dec. 2; is?! 1,193,650 Wildmah Aug. 8; 191's oTiiER REFERENCES Rohmann et. a1. Acorns; derPharmazieg" vol.

274 (1936), pgs. 110-426. 

